Environmental contaminants that interfere with endocrine function in humans and wildlife are a major regulatory concern. A current research need is to identify contaminants with this potential, and one approach to this is to develop methods for detecting endocrine disruption. Because thyroid hormone is critical to the process of amphibian metamorphosis, frogs are excellent candidates for use in assays which screen for chemical disruptors of thyroid function. The work proposed herein focuses on the thyroid axis. One significant thyroid hormone (TH)-induced changes that occurs during frog metamorphosis is a shift in the form of nitrogen excreted: from ammonia in aquatic tadpoles to urea in terrestrial or semi-terrestrial adults. We propose to follow urea synthesis in TH-challenged prometamorphic Rana catesbeiana tadpoles as an indicator of thyroid status, and hence of potential antithyroid activity. Our objective is to develop a rapid amphibian in vivo assay with which to predict potential interference of environmental agents with normal thyroid function. The dependence of anuran tadpoles on TH trigger urea synthesis provides a unique model system for the evaluation of suspected endocrine-disrupting agents across populations and species of vertebrates. PROPOSED COMMERCIAL APPLICATION: The GLEC-UWisc team requests support for a research project which we believe will produce: i) a reliable in vivo test method with which to screen for environmental chemicals that disrupt endocrine activity, and ii) a unique sentinel animal model in which developmental effects of potential endocrine disrupting compounds can be linked at the subcellular and whole-animal response levels. If successful, the test procedures proposed herein would eventually lead to commercialization of an effective and reliable in vitro environmental monitoring system for the identification of agents exhibiting the potential to disrupt normal thyroid function in wildlife and humans.